What Are Viruses?

A digitally colorized transmission electron micrograph (TEM) of the West Nile virus.

Credit: Cynthia Goldsmith, U.S. Centers for Disease Control and Prevention

Viruses are microscopic parasites, generally much smaller than bacteria. They lack the capacity to thrive and reproduce outside of a host body.

Predominantly, viruses have a reputation for being the cause of contagion. Widespread events of disease and death have no doubt bolstered such a reputation. The 2014 outbreak of Ebola in West Africa, and the 2009 H1N1/swine flu pandemic (a widespread global outbreak) likely come to mind. While such viruses certainly are wily foes for scientists and medical professionals, others of their ilk have been instrumental as research tools; furthering the understanding of basic cellular processes such as the mechanics of protein synthesis, and of viruses themselves.

Discovery

How much smaller are most viruses in comparison to bacteria? Quite a bit. With a diameter of 220 nanometers, the measles virus is about 8 times smaller than E.coli bacteria. At 45 nm, the hepatitis virus is about 40 times smaller than E.coli. For a sense of how small this is, David R. Wessner, a professor of biology at Davidson College, provides an analogy in a 2010 article published in the journal Nature Education: The polio virus, 30 nm across, is about 10,000 times smaller than a grain of salt. Such differences in size between viruses and bacteria provided the critical first clue of the former’s existence.

Toward the end of the 19th century the notion that microorganisms, especially bacteria, could cause disease was well established. However, researchers looking into a troubling disease in tobacco — the tobacco mosaic disease — were somewhat stumped as to its cause.

In an 1886 research paper titled “Concerning the Mosaic Disease of Tobacco,” Adolf Mayer, a German chemist and agricultural researcher, published the results of his extensive experiments. In particular, Mayer found that when he crushed up infected leaves and injected the noxious juice into the veins of healthy tobacco leaves it resulted in the yellowish speckling and discoloration characteristic of the disease. Mayer correctly surmised that whatever was causing tobacco mosaic disease was in the leafy juice. However, more concrete results eluded him. Mayer felt certain that whatever was causing the disease was of bacterial origin, but he was unable to isolate the disease-causing agent or identify it under a microscope. Nor could he recreate the disease by injecting healthy plants with a range of known bacteria.

In 1892, a Russian student named Dmitri Ivanovsky essentially repeated Mayer’s juicing experiments but with a bit of a twist. According to a 1972 article published in the journal Bacteriological Reviews, Ivanovsky passed the juice from infected leaves through a Chamberland filter, a filter fine enough to capture bacteria and other known microorganisms. Despite the sieving, the liquid filtrate remained infectious, suggesting a new piece to the puzzle; whatever was causing the disease was small enough to pass through the filter. However, Ivanovsky also concluded that the cause of tobacco mosaic disease was bacterial, suggesting the filtrate “contained either bacteria or a soluble toxin.” It wasn’t until 1898 when the presence of viruses was acknowledged. Dutch scientist Martinus Beijerinck, while confirming Ivanovsky’s results, suggested that the cause of tobacco mosaic disease was not bacterial but a “living liquid virus,” referring to it by the now outdated term, "filterable virus."

The experiments of Ivanovsky, Beijerinck and others that followed only pointed to the existence of viruses. It would take a few more decades before anyone actually saw a virus. According to a 2009 article published in the journal Clinical Microbiology Reviews, once the electron microscope was developed in 1931 by German scientists Ernst Ruska and Max Knoll, the first virus could be visualized with the new high resolution technology. These first images taken by Ruska and colleagues in 1939 were of the tobacco mosaic virus. Thus, the discovery of viruses came full circle.

This digitally-colorized image shows the H1N1 influenza virus under a transmission electron microscope. In 2009, this virus (then called the swine flu) caused a pandemic, and is thought to have killed 200,00 people worldwide.

Credit: National Institute of Allergies and Infectious Diseases (NIAID)

Structure

Viruses teeter on the boundaries of what is considered life. On one hand, they contain the key elements that make up all living organisms: the nucleic acids, DNA or RNA (any given virus can only have one or the other). On the other hand, viruses lack the capacity to independently read and act upon the information contained within these nucleic acids.

“A minimal virus is a parasite that requires replication (making more copies of itself) in a host cell,” said Jaquelin Dudley, a professor of molecular biosciences at the University of Texas at Austin. “The virus cannot reproduce itself outside the host because it lacks the complicated machinery that a [host] cell possesses.” The host’s cellular machinery allows viruses to produce RNA from their DNA (a process calledtranscription) and to build proteins based on the instructions encoded in their RNA (a process called translation).

When a virus is completely assembled and capable of infection, it is known as a virion. According to the authors of “Medical Microbiology 4th Ed.” (University of Texas Medical Branch at Galveston, 1996), the structure of a simple virion comprises of an inner nucleic acid core surrounded by an outer casing of proteins known as the capsid. Capsids protect viral nucleic acids from being chewed up and destroyed by special host cell enzymes called nucleases. Some viruses have a second protective layer known as the envelope. This layer is usually derived from the cell membrane of a host; little stolen bits that are modified and repurposed for the virus to use.

The DNA or RNA found in the core of the virus can be single stranded or double stranded. It constitutes the genome or the sum total of a virus’s genetic information. Viral genomes are generally small in size, coding only for essential proteins such as capsid proteins, enzymes, and proteins necessary for replication within a host cell.

Function

The primary role of the virus or virion is to “deliver its DNA or RNA genome into the host cell so that the genome can be expressed (transcribed and translated) by the host cell,” according to "Medical Microbiology."

First, viruses need to access the inside of a host’s body. Respiratory passages and open wounds can act as gateways for viruses. Sometimes insects provide the mode of entry. Certain viruses will hitch a ride in an insect’s saliva and enter the host’s body after the insect bites. According to the authors of “Molecular Biology of the Cell, 4th Ed” (Garland Science, 2002) such viruses can replicate inside both insect and host cells, ensuring a smooth transition from one to the other. Examples include the viruses that cause yellow fever and dengue fever.

Viruses will then attach themselves to host cell surfaces. They do so by recognizing and binding to cell surface receptors, like two interlocking puzzle pieces. Many different viruses can bind to the same receptor and a single virus can bind different cell surface receptors. While viruses use them to their advantage, cell surface receptors are actually designed to serve the cell.

After a virus binds to the surface of the host cell, it can start to move across the outer covering or membrane of the host cell. There are many different modes of entry. HIV, a virus with an envelope, fuses with the membrane and is pushed through. Another enveloped virus, the influenza virus, is engulfed by the cell. Some non-enveloped viruses, such as the polio virus, create a porous channel of entry and burrow through the membrane.

Once inside, viruses release their genomes and also disrupt or hijack various parts of the cellular machinery. Viral genomes direct host cells to ultimately produce viral proteins (many a time halting the synthesis of any RNA and proteins that the host cell can use). Ultimately, viruses stack the deck in their favor, both inside the host cell and within the host itself by creating conditions that allow for them to spread. For example, when suffering from the common cold, one sneeze emits 20,000 droplets containing rhinovirus or coronavirus particles, according to "Molecular Biology of the Cell." Touching or breathing those droplets in, is all it takes for a cold to spread.

A microscopic view of the Ebola virus.

Credit: CDC/Cynthia Goldsmith/Public Health Image Library

New discoveries

Understanding the relationships between viruses began with noting similarities in size and shape, whether viruses contained DNA or RNA, and in which form. With better methods to sequence and compare viral genomes, and with the constant influx of new scientific data, what we know about viruses and their histories is constantly being fine-tuned.

Until 1992, the notion that viruses were much smaller than bacteria, with tiny genomes was taken for granted. That year scientists discovered a bacteria-like structure within some amoebae in a water-cooling tower, according to Wessner. As it turns out, what they discovered was not a bacterial species, but a very large virus, which they dubbed Mimivirus. The virus is about 750 nm in size and may also have the same staining properties as gram-positive bacteria. This was followed by the discovery of other large viruses such as the Mamavirus and Megavirus.

“It is not known how these large viruses evolved,” Dudley said, referring to them as the “elephants” of the virus world. “They may be degenerate cells, which have become parasites of other cells (Mimiviruses infect amoeba), or they may be more typical viruses that keep acquiring additional host genes,” she added. Mimiviruses require a host’s cellular machinery to produce proteins, just like other smaller viruses. However, their genome still contains many remnants of genes associated with the process of translation. It is possible that Mimiviruses may have once been independent cells. Or they could have simply acquired and accumulated some host genes, Wessner wrote.

Such discoveries bring up new questions and open new avenues of research. In the future these studies may provide answers to fundamental questions about the origins of viruses, how they reached their present parasitic state, and whether viruses should be included in the tree of life.